The invention relates to the percutaneous absorption of solutions containing pharmaceutical compounds, cosmetics and toxic substances through permeable membranes such as human skin. In particular, the invention pertains to devices used to facilitate percutaneous absorption and improvements thereon.
Percutaneous absorption has recently become a standard technique in the drug industry for studying the flow of various active ingredient compounds into the human body through the skin. The technique most commonly used is known as the infinite dose technique in which human skin is mounted as a barrier between two well stirred fluid filled chambers. The compound under study is added to the solution on one side (donor) of the membrane and absorption assessed by serially sampling and assaying its concentration in the bathing solution (receptor) on the other side of the membrane. The apparatus used in the infinite dose technique is constructed of glass for easy visibility of the process by the researcher and to avoid the leaching of foreign materials into either the donor or receptor solutions.
A widely used and suitable apparatus for the infinite dosing technique of percutaneous absorption are diffusion cells available under the trademark Side-Bi-Side from Crown Glass Company, Inc., 990 Evergreen Drive, Somerville, N.J. 08876. This apparatus employs a pair of horizontally disposed glass diffusion cells having planar ground glass surfaces between which the skin membrane is held in a fluid tight joint and in communication with the interior of both cells. The cells are held together by a combination holding and clamping device. The unsupported area of the skin membrane, i.e., the surface area through which absorption takes place is defined by an orifice in the planar glass surfaces on either side of the membrane. Since the glass diffusion cells must be hand blown because of their configuration, it is inherent that the orifices vary slightly in diameter and roundness and consequently define a somewhat different surface area exposed to the membrane which adversely affects the accuracy of the absorption test results.
An alternative technique is the finite dose technique which utilizes an apparatus known as the Franz cell. Vertically disposed glass vessels are separated by the membrane and communicate through an orifice in each of the cells on either side of the membrane. The donor solution is present in the upper vessel and a receptor solution in the lower vessel. The Franz cell is constructed from blown glass and, like its counterpart used for the infinite dose technique inherently has the problem of slightly differing surface areas in the opposing orifices.